Pod Insights In Our Time Slime Moulds About this episode Melvyn Bragg and guests discuss slime mould, a basic organism that grows on logs, cowpats and compost heaps. Scientists have found difficult to categorise slime mould: in 1868, the biologist Thomas Huxley asked: ‘Is this a plant, or is it an animal? Is it both or is it neither?’ and there is a great deal scientists still don’t know about it.
But despite not having a brain, slime mould can solve complex problems: it can find the most efficient way round a maze and has been used to map Tokyo’s rail network. Researchers are using it to help find treatments for cancer, Parkinson's and Alzheimer's disease, and computer scientists have designed an algorithm based on slime mould behaviour to learn about dark matter. It’s even been sent to the international space station to help study the effects of weightlessness.
With
Jonathan Chubb
Professor of Quantitative Cell Biology at University College, London
Elinor Thompson
Reader in microbiology and plant science at the University of Greenwich
And
Merlin Sheldrake
Biologist and writer
Producer: Eliane Glaser
In Our Time is a BBC Studios Audio production
Transcript 10,309 words · 18 speakers
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1:30 Speaker 05 This is In Our Time from BBC Radio 4, and this is one of more than a thousand episodes you can find on BBC Sounds and on our website. If you scroll down the page for this edition, you'll find a reading list to go with it. I hope you enjoy the programme. Hello, if you've ever seen a mysterious white or yellow blob on your garden compost heap or on a fallen tree in the local park, you'll have come across slime mould. It's a single-celled organism that scientists have struggled to categorise. In 1868, the biologist Thomas Huxley asked, is this a plant or is it an animal? Is it both or is it neither? Despite not having a brain, slime mould is clever enough to find the shortest
2:11 Speaker 05 way through a maze, and scientists have used it to design rail networks, map dark matter in outer space, and research treatments for cancer and Parkinson's and Alzheimer's disease. With me to discuss slime mould are Eleanor Thompson, Reader in Microbiology and Plant Science at the University of Greenwich, Jonathan Chubb, Professor of Quantitative Cell Biology at University College London, and Merlin Sheldrake, Biologist, Writer and Research Associate at the Breyer University in Amsterdam and Oxford University. Jonathan Chubb, what is slime mould?
2:44 Speaker 00 It's actually quite a vague, fuzzy term that encompasses a lot of different species. They superficially seem very, very diverse, but there are some common features. Often a free-living, single-cell stage that goes around eating usually bacteria, but these organisms also have the ability to make spores, which are environmentally resistant and dormant, and can last for years before they germinate and generate single cells again. Now, there's a tremendous diversity. Some of these things are really a tenth of a millimetre in size, others are, can be a metre across. These are the big things you see on decaying wood. Some of the forms are incredibly beautiful, things like wolf's milk looks like German Christmas biscuits.
3:24 Speaker 00 There's also the dog's vomit, or better known as scrambled eggs mould, which looks exactly like that. It's a very, very successful type of species that has evolved multiple times during evolution, whereas as far as I'm aware, there's probably only one hominid branch. Even some bacteria have life cycles that resemble slime moulds, mixo-bacteria, which also have a single-cell stage which can aggregate to form spore-containing structures.
3:48 Speaker 05 How does slime mould relate to other organisms such as plants, animals and fungi?
3:54 Speaker 00 Putting aside the bacteria, if we can oversimplify the tree of life into two branches, which I'm going to get slapped for, but there's the branch that's a bit more plant-like and there's a branch that's a bit more animal-like and fungal-like. Now, slime moulds appear on both branches, so there are some that are a bit more plant-like and there are some that are a bit more animal-like. For example, the acracids are much more plant-like. They include certain human pathogens like neclyria, whereas the more animal-like ones include the amoeba zoa. That includes a big spectrum of acellular slime molds and cellular slime molds. But within these different groups, you have, for example, animal-like ones like amoeba zoa, looks very, very similar to plant ones like the acracids. So there's this motif, these features have popped up many times during evolution.
4:39 Speaker 05 How many species are there?
4:41 Speaker 00 I guess we probably don't know the extent that there's at least over a thousand. Many of the sort of acellular form.
4:47 Speaker 05 Yes. When did people come across them?
4:50 Speaker 00 Well, to the best of my knowledge, the first one named was wolf's milk in the 1600s. And it was as early as the 1700s, actually, that someone realised, this wasn't, initial reaction was this was some kind of fungus, but it wasn't until another century later that they realised, just based on the morphology, that it was something a bit different. It doesn't look like a mushroom.
5:08 Speaker 05 Yes. Thank you. Merlin Malishagre, can we develop where these slime molds are found and whether we see them and what they look like? Just give listeners a visual map of what they're sitting on, looking at or scraping off.
5:23 Speaker 06 So you'd find them in damp, often shady places, like on fallen logs or on fallen leaves when walking through a forest. And in different stages, they look like different things. Now, in the single-cell phase, you might think of them as being, if you had a microscope, as being some shape-shifting blobs, a little bit like your white blood cells that we have in our bodies. So shape-shifting, single-celled beings. But then they come together to form networks of slimy, tentacle-like veins, which could be pinkish, yellowish, orangey, and these networks are shape-shifting as well, but they're exploring, as a network, their environment. And they're the ones that look a bit like, sometimes can look like dogs vomits or scrambled
6:08 Speaker 06 eggs or tapioca pudding. But then they come together when they produce reproductive structures. You'd see those as very fine stalks, a few millimetres high, with a sphereish kind of structure balanced on top of the stalk, or a sausagey structure balanced on top of the stalk. And they're really remarkable looking. I mean, there are ones that look like little planets, or like single fish eggs, or like the seed pods of a very unfamiliar plant, or like corals that have erupted from small sacs. It's remarkable.
6:39 Speaker 05 There, we're told, there are around a thousand known species of slime mold, which fall into two main types, cellular and acellular. What are these? Let's start with cellular.
6:51 Speaker 06 Cellular slime molds spend much of their life living as single-celled organisms. And when times get tough, food gets scarce, they come together to form a multicellular structure. But the individual cells retain their identity as an individual cell. So it's a little bit like, imagine when you're playing with bubbles as a child. Those bubbles can sometimes stick together, but they remain. You can see the different bubbles in a kind of clump of bubbles. Now, the acellular ones, when they come together, because they also come together from a single-celled state into a kind of merged state. And when they come together, they form one giant cell. So it's a bit like those bubbles have joined to form one big bubble with one outer membrane.
7:32 Speaker 06 So it's quite a different way of leaving a single-celled state and coming into a merged state.
7:40 Speaker 05 Alan Thompson, let's keep banging on about this. Well, digging in might be a better way to put it. About this cellular slime mold. Trying to give the listener an idea of what they are. What's it made up of? Is it very similar to our own cells, their cells?
7:55 Speaker 07 Okay, so the cellular slime molds are the ones that we know particularly well, because there's an example of them, which we are using a lot in scientific research. So in the 1930s, an organism called Dictyostelium discordium was discovered on dung. And it's an amoeba, it's a eukaryotic cell. So it's a complex cell type like our own, which gives us an idea of the preservation of cell features over evolutionary time, because this is an anciently evolving branch of organisms that has cells that look very like our own.
8:30 Speaker 05 In the scheme of things, in your scheme of things, is it, does it surprise you that their cells are like human cells?
8:37 Speaker 07 No, because, so I'm really interested in what's maintained over evolutionary time in cells and so one sees it all the time. So bacteria, in fact, do many things that more complex cells can do. We always think of bacteria as being very simple, but they make up most of life on Earth. And then our epoxy eukaryotic branch, these complex cells that end with this tiny little twig of multicellular complex life with humans and animals on it. The thing that's special about the amoebi for us and makes them nice to use as a, as a model in the lab is because they're very like human cells in not having a cell wall. And we'll perhaps talk about the genetics as we go on.
9:16 Speaker 05 Yes. How does it behave at different life stages?
9:21 Speaker 07 Okay, so cellular slime moulds, as Merlin said, maintain a unicellular life habit, but they're able to join together to form a multicellular organism. So they have this amazing, fascinating life cycle where they can graze their prey microbes in the environment. So they go around engulfing bacteria as a food source. But then, as they reach very high numbers of cells and they start to run out of food, they signal to each other with a, with a chemical signal that tells them that it's time to move on and make spores. So single cells signal, and when one cell signals to another, another cell signals
10:05 Speaker 07 to other, and you get this propagating wave of chemical signals that then brings together waves of these single cells into a mound. And then the mound is able to sort of rise up and it topples over. And then, again, the amoebi, they sound so glamorous. We call this toppled over multicellular organism, we call it a slug. So every aspect of this is made to sound really unexciting, but clearly it is because we have these identical, single-celled organisms which come together to become a multicellular slug. And then this slug is a true multicellular organism which is able to move to a place where it can produce the next generation of spores. That's the point of the slug. But in doing that, we've
10:47 Speaker 07 Differentiated. So these independent living cells turn into different types of cell within the slug, and then they turn into a base, a stalk, and a spore head. And the amazing thing about that is that only some of the cells are in the spores. And so sacrifice becomes part of this dictyostelium lifecycle.
11:07 Speaker 05 When did they come into your area of knowledge about what was going on in life?
11:12 Speaker 07 I was given dictyostelium as a leaving present. When I left my, the lab where I did my postdoctoral research, I was working on a particular set of components of cells. And some very lovely colleagues in the dictyostelium community gave me some dictyostelium cells to take with me when I set up my own new lab. So I've had them for about 10 or 12 years.
11:32 Speaker 05 How have they behaved in that time?
11:34 Speaker 07 Uh, yeah, mostly okay. They are a really lovely organism because they're just so interesting. They're a really brilliant teaching tool. And when we have visitors to the lab who aren't necessarily scientists, they're a lovely thing to show them.
11:48 Speaker 05 What do you show them?
11:49 Speaker 07 Well, so, so the unicellular form of dictyostelium is not visible to the naked eye, but you can see where it is on agar plates, because if you put dictyostelium cells on to what we call a lawn of bacteria, it will graze those bacteria and produce very little sweet areas of grazed out bacteria, so zones of clearing that you can see on a plate. So that bridges the microscopic to the macroscopic. And then the multicellular stages, you can actually see with the naked eye. So you can see the stalk and spore head. So even though it's a microbe, visitors to the lab can actually see this thing.
12:20 Speaker 05 Jonathan, let's talk about the acellular kind. What's that made of and how does it behave differently from the cellular?
12:27 Speaker 00 I mean, it has a slightly more complicated lifecycle. Um, it can exist and feed. There's both this large thing that you see on rotting logs, but also a small cells which can either be amoeba like the cellular slime Moulds, or flagellate, which means it's a cell with a tail, think sperm cells. So I think the most remarkable phase of the lifecycle of this organism is this thing called the plasmodium, which is. These things are visible to the naked eye. Sometimes they can be a metre in diameter. They're these flat structures that you can see in the soil or on logs. These are, in some senses, quite unusual. Because normally when our cells divide, the cells copy the DNA. They segregate that into two nuclei and then the whole cell divides and each cell has a nucleus. But with these plasmodial or acellular slime moulds, you get the nuclear division.
13:12 Speaker 00 You get the whole growth. The cell itself doesn't divide. You've actually got a single cell which can weigh as much as 20 kilos. Which is, it's a very unusual strategy. We have some cells like that in our bodies. For example, muscle fibres are often fusions between multiple cells. But a single fibre is nothing like the scale of the acellular slime mould. So one of the other remarkable features about this, in a cell that large, moving material around is really rather hard. For example, in our bodies, we have a circulatory system that can move oxygen and nutrition around. In a single cell, that becomes a problem. But these slime moulds have developed an internal circulation which we call cytoplasmic streaming. So if you want to imagine how that works, imagine squeezing a sausage in the middle. And when you squeeze the sausage in the middle, the contents will move to the other side.
13:54 Speaker 00 So the cell has these proteins which basically wrap themselves around the tubes and they squeeze, much like if you were squeezing a sausage. And that causes flows of fluid along various channels within the cell.
14:05 Speaker 05 Dr Merlin, how does it make decisions? We said early on, they have no brain and yet they're very intelligent. Now, can you enlighten us on that?
14:15 Speaker 06 Well, I think it's helpful to think about some of the behaviours that we're trying to explain. So one of the very famous slime mould, the plasmodial or acellular slime mould behaviours is the ability to navigate labyrinths or mazes. And there are some very well-known examples of this with researchers recreating a Tokyo subway network. But others have done it with the network of Roman roads in Italy or the American highway system. Where if you put blobs of food, oats, they love oats, they're lab rats of the plasmodial slime mould world, love oats. So you can put oats on a big dish and then the slime mould will find the most efficient path between the oats. Having explored the dish, they can also find the shortest path between two points in a labyrinth. So the question is, how?
14:58 Speaker 06 Are they so good at searching space and navigating complex environments? Actually, they're so good at this. I have a friend who's an artist and he always got lost in Ikea stores, giant Ikea stores, and he had a stable of slime moulds at home. And he told me once that he'd made a scale model of the floor pan of the Ikea store, with all of the obstacles and routes that were available to him as a human with a brain. And he unleashed the slime moulds in the slime mould-sized Ikea store. And they were able to find the shortest path to the exit faster than he could, even though he had access to shop assistants to help direct him. So he would always say, "Look, they're cleverer than me." So the question is, how then can they navigate? You know, how can they find shortest paths? How can they do this? And it comes down to what Jonathan was saying,
15:41 Speaker 06 where these rolling waves of contraction move the cellular contents along these slimy vein-like protrusions, or sort of tentacles, a little bit like tentacles. And so when one of these arms or veins reaches some food, then it generates a stronger contractions along that arm of the network. And the stronger contractions move more cellular fluid along that arm. And the shorter the path, the more will pass along that arm. So what this means is that the stronger arms, the more, if you like, successful arms, the ones that are touching food, are strengthened at the expense of the arms that aren't touching food. And in this way, the slime mould can redistribute its body, orienting to new food sources and sensitively navigate through a landscape.
16:26 Speaker 05 I'm a bit taken aback by, I mean, this is the world you dwell in. This is a world that's completely new to me. It sounds almost like a magical world. Eleanor, again, and Jonathan, both of you, what can we gather about these slime moulds, social behaviour in communities? How do they communicate? How do they interact? Starting with you, Eleanor.
16:46 Speaker 07 Okay, well, if we follow on from the development of the unicellular to the multicellular organism, there are two particular features of that that we haven't mentioned so far. So one is the sacrifice that's involved. So 20% of a multicellular dictyostelium, in the case of this cellular amoeba, will become dead. Stork cells, so there's an element of self sacrifice. It's almost a philosophy of science that comes in here. How do you decide which cells will become the spore and which will become the stork cell? So the communication and control of that. And then the thing that really makes the hairs stand up on my arms still when I describe this is the presence of cheetahs in the community.
17:28 Speaker 07 So in the population of cells that all look the same as each other at the beginning, that aggregate into the multicellular organism, there are quite a lot of changes that can happen that will ensure that you become a spore. So some cells will make jolly well sure that they're in that spore head. And so we can learn a lot from dictyostelium about the messages that go between cells that make those things happen.
17:52 Speaker 05 How's that decision made? You say they decide to move there or there?
17:55 Speaker 07 Well, this is why knowing things about science makes the science sound more boring. So the self sacrifice and so there's another element of this, which is kin recognition. So dictyostelium spores have been found to be more likely to be relatives of each other so that they can recognize one another. And these features are surface features. So there's a green beard is the theory, isn't it? So the idea that you will choose somebody with a green beard to join your community. So a dictyostelium cell that recognizes a relative is more likely to aggregate with something that has that component on its cell surface.
18:32 Speaker 05 Do you want to carry this on, Neil?
18:33 Speaker 00 Not about greenbeards, but I think these cheetahs that seem to become spores and not sacrifice themselves. There's a limit to what the population can take of those. So they're very good at following the signals that allow them to become spores. But if you have too many of them, the population, you get an overall loss of fitness that is a break on how far they can actually permeate in a community.
18:53 Speaker 05 Yes. What is a cellular slime mold? What's it useful for? You look taken aback.
19:02 Speaker 00 I'm just trying to be diplomatic.
19:06 Speaker 00 I'll give a very personal answer, and possibly in the minority of one, but for me, I think the idea that it's intelligence is a very human view of the proceedings. I think, for me, it shows, from our perspective, very, very complicated behaviour using very, very simple rules. And I think that's what we have to take from this. What are those rules? And then think about how that can relate to more human types of questions. For example, I mean, you've got this vast network that's making this decision on which way to go or which path to strengthen.
19:40 Speaker 05 Are we talking about slime moulds or a road or what?
19:43 Speaker 00 I'm talking about the slime moulds mimicking the establishment of rail networks and things like that. And in practice, we would never set up a railway network like that. The way they do it is they send out this big flanks of material, almost at random. And that would be like building a railway every few metres and hoping that one of them would actually find the destination you're aiming for. But the branch that actually gets to the oatflake is the one that's stabilised and all the others are retracted. So in terms of designing rail networks, I'm not sure this is really that useful at all. But in terms of understanding what is effectively a complex behaviour and understanding the basic rules of that, I think it's extremely useful. I mean, our brain is also just a network of cells that are communicating and they're using similar types of, basically the same types of cell
20:26 Speaker 00 biological processes to underline the structure of this network. Just our networks are bigger and more complicated and have more sub-departments.
20:32 Speaker 06 Yeah, so the way that they find these, or navigate space and find these routes, is very different from the way that we would do this because we're centralised organisms. Now, if we were dropped off in the middle of a desert and we had to go and find water, we'd have to pick one direction and we'd try that one direction. We might be successful, we might not be. And we'd have to keep looking one route at a time. But slime moulds, these acellular slime moulds, a bit like fungi, are able to grow out in all directions at once, which means they can search space quite efficiently. But when they get to the point of interest, say it was us in a desert finding water, but for the slime moulds finding oatflake. Then they can strengthen that line and retract the parts of their inquiry which didn't lead anywhere. So it's just a different way of navigating space.
21:17 Speaker 06 And so what that means is that you can, when researchers have done these experiments where they've recreated road networks, or there are some that have used slime molds to calculate the fastest fire evacuation routes from buildings. What you're doing is you're asking the slime mold to find the shortest path to the oat fleck, which you've positioned at the exit if you're trying to find the fire exit. So we might design in a slightly different way, but these are partly demonstration and partly a way of trying to understand these different strategies that organisms have to navigate a changing and varied world. And what's amazing in these cases, to me, is that they're able to solve this kind of problem without a centralized place to do so. We're used to thinking of our bodies in terms of centers. We have heads and we have hearts. We make capital cities.
22:02 Speaker 06 We have heads of state. The centralization runs all the way through our societal metaphors. But slime molds don't. Their coordination takes place a little bit everywhere at once and a little bit nowhere in particular. And so I think it's important as an example, as a way of life, because it illustrates that one doesn't need a brain to solve problems.
22:21 Speaker 05 You mean, none of us need a brain to solve problems?
22:25 Speaker 06 So I think one of the things this illustrates is that we're used to thinking about brains as being totally key to problem solving, because we have brains and we're proud of our brains, and rightfully so. But there are lots of ways to solve the problems that life presents. And slime molds illustrate some of these other ways. And in jolting us into remembering the many ways that there are to solve problems, I think they've done us a great service, at least done modern science a great service.
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24:37 Speaker 03 Hello, Misha Glennie here. Did you know you can get episodes of In Our Time 28 days early with a subscription to the BBC website and app? Just head to bbc.com/subscribe to find out more.
24:55 Speaker 00 I think there's a lot of examples where even some of the more complicated emergent behaviors that are shown by the cellular slime molds are happening in our bodies and during development. The primary example would be how the cells talk to each other when they're in the single-cell state. So, they talk to each other with this chemical called cyclic AMP. And that chemical is like a relay. So, one cell releases cyclic AMP, and the next cell sees it and goes, "Oh, I'll release cyclic AMP." And then that passes along this chain. So what happens is a bit like one of those next And waves you get at a football match, where everyone just sees what their neighbour does and it goes around the whole stadium. So you get these waves and waves and waves propagating across the population. So that type of emergent behaviour is occurring in several aspects of our own physiology. So if you have a cut, the cells that are surrounding
25:39 Speaker 00 the edge of the wound will have similar types of wave as they coordinate the closure of the wound. You see similar patterns, these waves, certainly on a two dimensional surface, they form these beautiful spiral patterns. So you can see these, just making recordings of electrical activity in the brain, you see very similar shaped patterns of activity. The contractions within our heart show the same types of what we call excitable behaviour, where you have one cell signaling to the next and so on and so on and so on.
26:03 Speaker 05 Well, can you develop that a bit?
26:05 Speaker 00 I would say that if you wanted to studying a lot of fundamental problems about, certainly from my perspective developmental biology and how you build structures in an organised fashion. Biologists like to think of some sort of central control element that directs things or some sort of blueprint. But the more and more we look at how embryos develop, there's so much more which is about self organisation and adaptation to the environment and almost finding a structure and then modifying it to suit the environment and to suit the associated structures.
26:32 Speaker 05 Do you want to add to that?
26:33 Speaker 06 Yeah, I think it's, I mean, it seems to me that one of the central problems of biology that's been around for a very long time is how how parts come together to form complex holes and how these holes can be nested within even greater holes. And you think about our bodies, we have cells of certain types which come together into tissues, which come together into organs, which come together into a coordinated feeling, wild, wet you, you know, and that can explore the world and sit here talking about life. So these are nested systems of organisation and it's such a puzzle on so many levels, you know, how do these cells communicate with each other, how the cells know what to become, when to stop becoming what they're going to become, how do they then coordinate with all the other cells? So in a sense that this is a big persistent question in biology, I think slime molds, especially
27:18 Speaker 06 the cellular slime molds can really help us to have a kind of model system where you can see the journey from a cell into a complex morphology, which can differentiate into different cell types and regulate as an integrated organism. And so much of science is playing around really. And I think they can really contribute to this enduring question of how do organisms acquire form and how do organisms develop into complex forms?
27:44 Speaker 05 Jonathan, can we talk about how useful these slime molds have proved to be for scientists?
27:50 Speaker 00 I'll talk about the cellular slime moulds if that's all right.
27:52 Speaker 05 That's right, yes.
27:53 Speaker 00 So I'm, I think a lot of people who study slime moulds, study them because the, in the single cell stage, the cells look very much like the cells of our immune system. Cells like neutrophils and macrophages, the job of which is to maraud around the body looking for bacteria and other things to eat and, and going to a wound and stopping infection getting in. It's very difficult to study these cells such as neutrophils and macrophages. You can take them out of your blood, but they're often dead within a few hours. Whereas you can, slime moulds just grow on the bench. But actually, the overall cells themselves, the way they move, even the chemistry, the biochemistry, explaining why they move is highly related to these immune cells. And in particular, the two features of immune cells that matter, which is finding your prey, which is identifying where the bacteria are, and which, a process we call chemotaxis,
28:38 Speaker 00 and then killing the bacteria, eating the bacteria, which we call phagocytosis. So cellular slime moulds are experts at this.
28:45 Speaker 05 Can we talk in a little more detail about how scientists are using these cellular slime moulds to research diseases like cancer, Alzheimer's, Parkinson's, epilepsy, bipolar disorder? They seem to be everywhere and they seem to be everywhere effective. Can you give us a summary of that?
29:03 Speaker 07 Yes, I can. So there are probably three parts to this answer, and the first is probably the most boring part, but it is what Jonathan has alluded to, which is that we can grow the cellular slime mould, the amoeba dictyostelium, very easily in the lab. And we have strains of dictyostelium that we can grow in flasks shaking about in an incubator, which means we can grow lots of cells, which means that we can look at the chemistry of something much more easily than we could have a look at a nerve cell or a component of us. There's a second part, which allows us to, to really start to study complex things like disease in us, which is that dictyostelium was sequenced very early in the sequencing era. And so it became apparent very soon that dictyostelium, through a slight freak of
29:46 Speaker 07 evolution, actually has retained an enormous number of genes that correspond to our own. So the cellular equipment that dictyostelium has.
29:54 Speaker 05 A freak of evolution.
29:55 Speaker 07 Well, yes, so the reason I say that is because yeasts are very nice. Karyotic microbe, they have complex cells like ours, they're fungi and you can grow them very easily in the lab, but they seem to have lost a lot more of the human-like genes. Although up on the tree of life, I think even a dictyostelium biologist would agree that you would think that fungi will be more similar to human cells, but it just happens that dictyostelium has an unusually large number of genes that correspond with ours. And therefore, if you're interested in a particular disease pathogenesis, how a disease progresses, you can study it in dictyostelium by looking at the gene in the amoeba that goes wrong in human disease.
30:36 Speaker 07 And then the third part of the answer is that dictyostelium also has many parts of the way it behaves and its life cycle that are analogous to aspects of human disease. And I can list those if you like, or you can come, okay? So some, some things that correspond really nicely with human disease in us are the migration, the motility of cells. So that's relevant to cancer cells when they metastasize. So we can study the adhesion of the amoeba dictyostelium to a surface and why it adheres and why it doesn't. And we can study how cancer cells might move and spread using that system. The migration of cells is also seen in wound healing. So we can study, you know, the good and the bad of disease.
31:21 Speaker 07 I mean, there are, there are many aspects of dictyostelium that mirror disease, but the neurodegeneration, one that you mentioned, so Parkinson's and Alzheimer's, it has a couple of things where it's particularly relevant. In the case of Alzheimer's, dictyostelium seems to be very resistant to the protein aggregation, the plaque formation that's very characteristic of Alzheimer's disease. So some research is trying to find out, you know, what aspects of that you might employ to fight Alzheimer's. And then in terms of Parkinson's, which is the second most common neurodegenerative disease of aging, and many diseases of aging in humans come down to a problem with the energy generation of the cell. So the mitochondrion, the compartment of the cell that makes energy.
32:02 Speaker 07 And dictyostelium has a, a sort of fun feature, which is that if it has a defect in its energy generation, you will often see
32:10 Speaker 07 Dictystelium amoeba cells that can't respond to light very well. And they don't develop very well in their life cycle. And when they do develop, they often have little short fat stalks. And so if you have dictystelium that has these particular appearances, characteristics. It's been found that the genes that go wrong are often ones that go wrong in human neurodegenerative diseases as well. So we can explore those cell and genetic pathways in dictystelium a whole lot more easily than we can in a human cell.
32:40 Speaker 05 These strange little objects seem to cover most of the territory, don't they? Jonathan, computer scientists are using them to, they're sending them up into space. Who's going to take that on?
32:51 Speaker 00 I can have a go. The experiment I want to see done in space hasn't been done, which is to take a huge bucket of dictystelium spores or slime mold spores up into space and just release them and see do any live ones come back? And can they actually see life somewhere on earth? If we can label them and somehow can we actually get spores to come through the atmosphere? I think this could be a useful way of colonizing future worlds. It's a bit far out, but in terms of what's actually been done, both the cellular and acellular slime molds have both been up to space. The cellular slime molds 20 years ago went up on a NASA expedition to look at the effects of both gravity on their, the formation of their three dimensional structures, but also the effects of ionizing radiation on the organism. And actually they'd found that the cells didn't really care very much. They did their thing.
33:34 Speaker 00 More recently, acellular slime molds, Faizaram, have been on the International Space Station again to look at the behaviour of these very large cells in a low gravity environment. It was found that they have a more 3D like structure, whereas if you see them on a log, they tend to be quite flat. So there was something learnt about that. I mean, I think the most important thing is that these cells, they like surfaces. So I'm not sure how informative for the biology of this organism this actually is, but it was quite interesting. It was a massive collaboration with a lot of schoolchildren who made the earth side measurements of Faizaram.
34:06 Speaker 05 How important is a slime mold for very small microbes?
34:09 Speaker 07 Cellular slime Moulds can teach us a lot about microbiology. They're a really good example of the complexity of microbial life. So I think perhaps there's an idea in general that that we're incredibly complicated and super beings, but when we look at something like dictyostelium, we start to understand just how sophisticated microbial life on earth is. And if we look at the tree of life whole, not as Jonathan did at the start, but we really, if we include the bacterial groups and we see how early off the tree of life, the amoebi that include dictyostelium branch off, and we see that the fungi and the algae and animals are at the top.
34:51 Speaker 07 We have this illustration that even something as sophisticated as dictyostelium is a microbe and it's on a microbial branch. The world is microbial and dictyostelium also lets us study what's microscopic because we can see stages of dictyostelium. So I guess it makes that microbial world visible to us as well.
35:10 Speaker 05 Jonathan, what do we not yet understand about slime Moulds?
35:15 Speaker 00 I think for the last forty or so years, dominated by technologies of molecular biology, we've amassed a huge amount of data and we're drowning in data, really. I think the challenge really is to try and make sense of all that, to try and integrate all that information. And my feeling is that, and this is a problem for slime mold research as well, but I feel that slime mold research has a manageable level of complexity where we can actually answer big questions without drowning in information. So I think the challenges I see, for example, are how do cells really integrate information? We know we have some good answers for how cells can integrate information from one signal, but cells are bathed in different signals all the time. They're seeing, it's like walking down Houston Road during rush hour.
36:00 Speaker 00 There's all these sights and sounds that are completely hitting them and how does that single cell process all that information? I think that seems to be the biggest challenge. I mean, more generally, I would say what you have here is a very, very successful
36:15 Speaker 06 Mode of living, this idea that single cells can either aggregate or generate a very large cell which makes spores. A beautiful example of this is, some of you may have seen the Terminator movies with Arnold Schwarzenegger. So, in the later generations of the Terminators, there are Terminators, they're made of liquid. So when their arm gets cut off, it forms this pool of liquid on the floor, which over the next thirty seconds to a minute, regenerates the arm. So it gives the good guys time to get away. But, you know, what are the limits to this type of self-organizing emergent behaviour? I mean, what, could it build more complexity? Is there a restriction on this complexity? It's obviously a very successful form of life, maybe it doesn't need to, it's very adaptive. I mean, that would be the more philosophical question, is, you know, what are the limits to this approach? And can we evolve something that could have more functionality?
36:59 Speaker 05 Melanie, I'd like to come back to something we touched on earlier, and I think listeners will be very intrigued to know, how do slime moulds change our understandings of massive things like memory and intelligence and individuality? We said at the beginning, they were without brains, but they seem to solve brain problems more oppressively than human intelligence in some ways. So can you give us your view on that?
37:23 Speaker 06 I think there are a few very interesting ways that they teach us about memory. And the a-cellular slime moulds in their plasmodial stage, so these slimy vein-like networks, have been challenged with all sorts of experiments. And in one memorable experiment, these networks were given an opportunity to cross a salt bridge, a salty channel, leading to a plate of food, or something delicious. And they didn't like to cross the salty channel, that it's salty, it's uncomfortable, it's not something they would choose to do. But over time, they explore, and over time, the ones that explore, reach the plate of food on the other side of the salty channel. Now, given the chance to explore the similar sort of obstacle course again, the ones that had crossed the salty channel to get to the food...
38:09 Speaker 06 They were quicker to cross the salty channel again. They had somehow learned and had an enduring memory that this was something that they could expect in their way, some kind of response where they'd remembered that the salty channel was something that might lead to food. So what's interesting then, it's interesting first of all that they can learn in that way, associative learning, we might think of it as, although there are potentially other ways to think about it. But then, when a slime mold that had learned was exposed to a slime mold that hadn't been exposed to the obstacle course, so you might say a naive slime mold, and they were given the chance to form a connection for around an hour, and then separated, the naive slime
38:50 Speaker 06 mold was quicker to cross the salty channel to the plate of food. And what's funny about that is that this, we usually think of memory as needing a subject, you know, the subject, in our case is us, in my case, me, is the owner, if you like, of memories, the seat of memories, and it's something to do with my past experience that I'm recalling when I have a memory. But in this case, a self, the slime mold, naive slime mold, which had not experienced this challenge, did have the memory. The memory had somehow been transmitted from slime mold to slime mold, without the second slime mold, the naive slime mold, needing to have that experience. So I think that raises all sorts of questions about selfhood, about the nature of memory,
39:32 Speaker 06 of how memories might be transmitted between different organisms, and certainly dislodges some of our assumptions about memory that we might have if we stood only looking at humans and other animals with brains.
39:44 Speaker 05 Does it dislodge our ideas of intelligence? What you're talking about is something that if we weren't using the word slime mold, we'll say, that's very intelligent, that's very intelligent, and so on. It's these slime molds, like, these sort of pre-slugs that are getting in the way of me accepting that, I accept it, of course I do. It's imagining how they can do without a brain, as you keep saying, what they do, which in some ways sounds as if it's as intelligent or more intelligent than things we do.
40:14 Speaker 06 I mean, the word intelligence has undergone some discussion in recent years within biological fields, and it used to be a word that was applied to the sort of behaviours that humans can do, because the cognitive science has placed humans at the centre of their inquiry, naturally, because we try to understand ourselves. But over time, definitions of intelligence have deepened and expanded. And now, I subscribe to the view that intelligence refers not to something, it's not a property that one has or one doesn't have, that there are behaviours which you might think of as intelligent behaviours, different types of intelligent behaviour, that one might possess to a greater or lesser degree. And you might think of those as being able to make decisions between alternative courses of action, you might think of them as being able to adapt to changes in one's environment, you might
40:59 Speaker 06 think of them as the ability to solve certain kinds of problem. And when you think about it like that, almost all organisms have some degree of intelligence, because all organisms have some degree of intelligent behaviour, because they all live in a changing world, we all live in a changing world, we all have to solve different kinds of problem. Now, the kinds of problem that humans have to solve are quite different from the kinds of problem that a plant has to solve. So, we might miss the ways that plants are sensitively responding to their environment in problem-solving ways, if we only use human categories. So, I'm very interested in how that debate has expanded and how it leads us into thinking about life from the perspective of different organisms, and stepping outside our own human-centric perspective.
41:38 Speaker 07 Can I add something to that?
41:39 Speaker 06 Yes, sure.
41:40 Speaker 07 The idea that an organism can know how related it is to its neighbours is something that we can see happening in these amoebae, but we can also see it in bacteria. So, if you've got different subspecies of a very common skin bacterium called Staphylococcus aureus, a community of those bacteria will know how-
41:58 Speaker 05 You're talking about millions here, millions of bacteria.
42:02 Speaker 07 Millions of bacteria will know whether their neighbours are related to them or not, and will make decisions according to the relatedness of the bacteria around them. There's another bacterium called Pseudomonas aeruginosa, which is the one that infects you when you have cystic fibrosis, but it's a very common environmental organism. Iron is often a limiting nutrient in the environment, and Pseudomonas aeruginosa will cooperate and produce a chemical that will grab the iron together as a community. So, again, just this idea of intelligence and cooperation, it's our definition that's problematic as we learn more and more about life on Earth.
42:39 Speaker 05 We're coming to the end now, but still, Eleanor, what do you think this investigation into the effectiveness of slime Moulds has had on the whole? How has it changed your view of how the world works?
42:51 Speaker 07 Well, I have, I have two microbiology degrees, so I, I've spent decades thinking in terms of the complexity of life on earth, but I, I love to think that our, well Merlin's done an amazing job telling the world about fungi and how complex and interesting and widespread they are, and it would be great if an exploration of the amoebi, which sounds perhaps even less exciting, would make people understand that we live in this fantastic microbial world, all life on earth is really microbial, and complexity in life started really early on the evolutionary tree, and we can use it to simplify our understanding of our own bodies in, in many ways. So I, I'm a great proponent for microbiology, and
43:35 Speaker 07 I, and I hope on that level that our understanding of these systems helps people appreciate the world that we're living in a bit better.
43:43 Speaker 05 Jonathan?
43:44 Speaker 00 From my perspective, I, I think that, I've been working with slime Moulds now for nearly thirty years. Before that, I was very, very welded to this almost religious view of embryology and developmental biology, that there is a blueprint or a pre-plan for how an embryo is constructed. And I think I'd probably still be there without that exposure to a completely different way of doing things. In fact, for about twenty years, most people who worked on slime Moulds believed in the blueprint model. I think revolutions in mammalian biology have very much allowed us to relax and believe what we want to believe again, which is that I think emergence is really, really important.
44:19 Speaker 05 Finally, last word from you.
44:21 Speaker 06 I study fungi a lot, which are network-forming organisms that are capable of complex behaviours in this kind of bottom-up way that we've been discussing with slime Moulds. And for me, slime Moulds make it so clear, they're really poster organisms for kind of brainless problem-solving, in my mind. And they illustrate something really fundamental, because so many biogeochemical processes, so many processes that have really shaped the world over hundreds of millions of years, have been overseen and conducted by network-forming organisms that have analogous behaviours. And so slime Moulds for me are a gateway into a whole other way of being, a whole way of living, which is not only vitally important today, but which has shaped the very conditions for our existence.
45:02 Speaker 05 Well, thank you very much. Thanks to Merlin Sheldrake, Alan Thompson, and Jonathan Chubb. Next week. We take a break and we'll be back on the 16th of January with the Battle of Baumein 1792, which saved the French Revolution and cemented the Marseillaise as the national anthem of France. Thanks for listening.
45:20 Speaker 12 And the In Our Time podcast gets some extra time now with a few minutes of bonus material from Melvin and his guests.
45:27 Speaker 05 What did you feel you didn't have time to say that you liked to have said? Jonathan, what about you?
45:32 Speaker 00 Is it okay if we talk about slime mold sex?
45:34 Speaker 05 I think we'll give that the green flag.
45:37 Speaker 00 So it's probably more arcane than anything in a Julie Hooper novel, and I'll be brief.
45:44 Speaker 05 You know what you do.
45:45 Speaker 12 No, fungi are the worst.
45:48 Speaker 05 One, two at a time. Jonathan.
45:51 Speaker 00 So slime molds get in the mood usually when it's dark and they're starving, but in submerged conditions. So what that encourages them to do is that, I should start by saying there's actually three mating types in the slime mold I work on. So that's one more than us. But it almost doesn't matter which mating type you are, but when they decide that they're going to mate, they all come together and form this giant cell. And then in that process, you get the nuclear fusion, which characterizes any normal mating process. And then the fused nuclei segregate into little cells on their own. And then they proceed to eat all the cells around them. So this would be like this first matrimonial event being eating the whole village. So it's completely bizarre. Anyway, after eating the whole village with
46:35 Speaker 00 all that nutrition, they then form another type of resistant spore called the macrocyst, which then sits around for a few months until conditions are better.
46:42 Speaker 05 And what about you, Melvin?
46:45 Speaker 06 Well, I think that slime molds are beautiful gateways into some of the so many strange ways to be alive. And there are so many phenomena, and even in animals, that are reminiscent of some of the things that slime molds can do. For example, with flatworms, you can teach flatworms tricks. They can be taught to learn something. If you cut off their head, they regrow a whole new head, a whole new brain, and they can still remember tricks that they've been taught with a new head and new brain. So the question is, where is the memory in their body then? Moths and butterflies can learn a new food plant as an adult. So they can, they'll lay their eggs on a new food plant. And with moths and butterflies, caterpillars can be exposed to, for the first time to a new food plant.
47:29 Speaker 06 And then they completely liquidate their body and reform into an adult butterfly or moth with wings. And they can somehow remember the new food plant from this earlier stage of their life, despite the fact their bodies got undergone a massive liquidation and reconstruction and reformation. And so this is a kind of phenomenon, I think, opens our eyes a little bit more to the wild weirdness of life and perhaps dislodges us a little bit from some of these more top-down views of development, like Jonathan was talking about earlier with this kind of, the single blueprint highway to an outcome approach. There are lots of ways to get where one needs to get in life.
48:10 Speaker 06 And so slime molds open up that world for me and I think are really helpful reminders of the many ways there are to be alive.
48:18 Speaker 07 There's another aspect to the, you know, the weird and wonderful behaviour of amoebi that we've discussed today, that is how many aspects cross over with the fungi and with the algae. And these are some of the really difficult groups in evolution that we've had real problems classifying them. And today there are still arguments being resolved as we get gene similarity across these different groups. But I think that almost the difficulty in understanding amoebi and understanding fungi and understanding algae and what they are, is a really nice way of illustrating that all of life on earth originates from one cell, you know, one point. So life on earth has evolved from a cell that had a set of properties.
49:01 Speaker 07 And even though we have convergent evolution in many characteristics across, we see similarities in many organisms that's not evolutionary preservation of genes. But this continuum of behaviour that we see in the amoeba and across other groups really shows us that similarity.
49:15 Speaker 00 I guess probably the last thing I would want to say is that because these modes of existence have occurred so many different times during evolution, they're obviously doing something right. So what is that and can we learn from that?
49:27 Speaker 05 You think they're on the path towards perfection?
49:32 Speaker 05 That's a bit of a jump, sorry.
49:34 Speaker 00 Well, we can roll with that. There's certain things that they do do very well. One is there's clearly distributed thinking. It's not, I'm the leader, you do this. When they've exhausted their local environment, they form spores and just chill out for a few years and wait for the conditions to improve. You know, there's a limit to how much they can exploit.
49:52 Speaker 06 That's interesting when thinking about fungi and what evidence we have of fungi in the past. You see fungal networks which look very, very similar to modern fungal networks. So the morphological long history of fungi is one of consistency. It's as if they hit on this way of life very early and haven't needed to do much to it. But look at the fossil record of animals and you see a huge variation in form. There's a total like coco fluorescence of biological possibility in different ways of being, different numbers of teeth and wings and all sorts of weird and wonderful ways to be. And so, yeah, I like the idea that they stumbled on this quite early on and haven't needed to do that much over all of these hundreds of millions of years.
50:36 Speaker 07 In our lists of the utility of dictyostelium in the lab, so the uses of it maybe in biomedical science, we didn't talk about drug development and understanding how drugs affect our bodies. So of the many features of dictyostelium that are useful, it having so many components of cells that are the same as ours mean that if you have a drug and you treat dictyostelium with a drug, you can sometimes work out the mechanism of action. So that's been done in bipolar disorder and epilepsy. And looking at an epilepsy drug like sodium valproate, one of our colleagues has tried to screen new drugs that are less toxic using dictyostelium. So there's a whole area of not using animals for research here.
51:21 Speaker 07 So if you've got new drugs that target the same pathway that sodium valproate targets, there's a high chance that they might be just as toxic as that is and perhaps produce birth defects in the way that that drug can do. And then if you find antiepileptic drugs that don't target that pathway in dictyostelium, you've saved yourself a whole load of very, very early biological research, admittedly. But it can be a really useful first screen for the genetics, the molecular biology, the protein biology, before you start to move, you know, higher up.
51:55 Speaker 05 Have you anything to say about that, Jonathan? I mean, I'm fascinated by the fact that this thing has influence on these massive diseases, which you keep reading about very difficult to cure. We've gone one step forward in Alzheimer's, we don't quite know where we are with this, that and the other, and I just wondered how they went about it.
52:13 Speaker 00 I can give an example of quite a devastating condition called acute respiratory distress syndrome. Now, that's caused by, it's an inflammation of your lungs, and this is caused by immune cells being overactive. So what happens when you, normally, if you've got healthy lungs, then it's not usually an issue, but if you have inflammation in your lungs caused by smoke usually, or vomit or something like that, then the first cells that get there are these immune cells called neutrophils. Now, they're a bit like, imagine suicide bombers, basically. They go there and they kill, they start acting, and if there's any bacteria around, they'll eat those bacteria, but they're also pretty non-specific, so they'll start causing a lot of damage to the tissue. And of course, when you have more damage to the tissue, you get even more inflammation, which means even more immune cells, so then this whole thing just sort of cascades out
52:58 Speaker 00 of control. So neutrophils on their own, for example, if you have a cut and you have this sort of little yellow bit of pus, that's what they are, it's not usually a problem, because what happens is that the next generation of, or the next round of immune cells, they're called lymphocytes, come in and they're much more specific, so they can mop up the bacteria without causing tissue damage. They also send signals out to the neutrophils saying, "Go away, go away." So the whole wound then becomes a much more controlled environment. Now, one of those signals, it's called APR, is something that the slime molds use, so in the capacity they use it, is when they're feeding on a nice plate of bacteria, when the cell number increases so much and the amount of bacteria drops, they start releasing this chemical and it's basically saying, "Disperse, disperse, disperse."
53:41 Speaker 00 And it's the same molecule, and this molecule was identified in the slime mold and is now being used in clinical trials for this horrible respiratory condition.
53:47 Speaker 05 Well, thank you all very much. That was a cracker, thank you all very much.
53:51 Speaker 13 We really need a drink after that mind-blowing discussion.
53:54 Speaker 05 Yes.
53:55 Speaker 13 So what would you like, Marvin, tea or coffee?
53:57 Speaker 05 I thought you were going to say a whiskey or a... Jim and John would go down there. I don't know.
54:03 Speaker 13 And then what would you like?
54:05 Speaker 00 So you need the food, they need to...
54:07 Speaker 05 I'd like a tea.
54:09 Speaker 13 And then a plate of coffee.
54:13 Speaker 14 In Our Time with Melvyn Bragg is produced by Simon Tillotson and it's a BBC Studios audio production.
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